Neurobiology of Addiction - University of Utah · 2019-08-19 · Neurobiology of Addiction. Tiffany...
Transcript of Neurobiology of Addiction - University of Utah · 2019-08-19 · Neurobiology of Addiction. Tiffany...
Neurobiology of Addiction
Tiffany Love, Ph.D.Department of Psychiatry
The University of Utah
What is Addiction?
• Addiction is a chronic, relapsing, and treatable brain disorder. • Compulsive drug seeking and use in spite of serious
consequences
Three Stage Model of Addiction
Koob & Le Moal 2008
Stage 1Binge /
Intoxication
Stage 2Withdrawal /
Negative Mood
Stage 3Preoccupation / Anticipation
Three Stage Model of Addiction
1. Binge / Intoxicationo Associated with positive
reinforcement & motivational learning
o Associating cues with reward delivery
Stage 1Binge /
Intoxication
NAc
VTAe.g., Cat on Catnip
Dopamine
DopamineReceptor
Nucleus Accumbens Ventral Tegmental Area
*
What does ↑ dopamine signal?↑ Value of future reward / of
work to gain the reward ↑ Motivation to obtain reward↑ WANT
– Evolved out of survival –
Dopamine
DopamineReceptor
Nucleus Accumbens Ventral Tegmental Area
*
Dopamine is released in response to many types of rewards
Di Chiara and Imperato, PNAS 1988, Slides NIDA
Drugs of abuse can be more reinforcing than natural rewards
Drugs of abuse can release up to 10 times the amount of DA that
natural rewards do
Overstimulation of the reward circuit:
o Leads to an increase in the drive to obtain drugs over natural rewards
DA
–DA
DA neurons will eventually fire in response to cues that predict the reward
Conditioned stimuli paired formerly paired with the drug elicit DA
release
o Trigger cravingo Increase motivation
to seek out drugo May lead to binge
use
Three Stage Model of Addiction
2. Negative Affect & Withdrawalo Associated with
negative reinforcement and increases in stress
Koob & Le Moal 2008
Stage 1Binge /
Intoxication
Stage 2Withdrawal /
Negative Mood
Stage 3Preoccupation / Anticipation
Neuroadaptations as a result of prolonged drug use: Dopamine
• At baseline, dopamine receptor concentration is reduced to compensate for the frequent, large dopamine surges elicited by drug use
Control Drug AbuserVolkow et al 2009
Reward Circuits
Normal
Prolonged Drug Use
Dopamine
DopamineReceptor
Reward Circuits
HIG
H
BaselineNormalFeeling
*Elevated Reward
Threshold
Reward Circuits
Normal
Prolonged Drug Use
Dopamine
DopamineReceptor
Reward Circuits
HIG
H
BaselineNormalFeeling
*Elevated Reward
Threshold
Stress Systems DysregulatedHypo-
thalamus
Anterior Pituitary
Adrenal Cortex
HPA/Stress Axis
CRF
ACTH
CORT
DYSPH
OR
IA
BaselineNormalFeeling
*Negative Motivational / Affective state
Low CRF
High CRF
Stress Systems DysregulatedHypo-
thalamus
Anterior Pituitary
Adrenal Cortex
HPA/Stress Axis
CRF
ACTH
CORT
DYSPH
OR
IA
BaselineNormalFeeling
*Negative Motivational / Affective state
Low CRF
High CRF
Stress Systems DysregulatedHypo-
thalamus
Anterior Pituitary
Adrenal Cortex
HPA/Stress Axis
CRF
ACTH
CORT
DYSPH
OR
IA
BaselineNormalFeeling
*Negative Motivational / Affective state
Low CRF
High CRF
Long-term Result of Neuroadaptations
Time
Amount of drug needed to feel
normal
HIG
H
DYSPH
OR
IABaselineNormalFeeling
Three Stage Model of Addiction
3. Preoccupation & Anticipationo Associated with
changes to executive functioning
Koob & Le Moal 2008
Stage 1Binge /
Intoxication
Stage 2Withdrawal /
Negative Mood
Stage 3Preoccupation / Anticipation
Normal
STOP
Control
Automatic
Iowa Gambling Task
Iowa Gambling Task
GOOD• WINS: Small,
Frequent• LOSSES: Moderate,
Rare
$
Iowa Gambling Task
BAD• WINS: Large,
Rare• LOSSES: Large,
Frequent
$
Iowa Gambling Task
GOOD• WINS: Small,
Frequent• LOSSES: Moderate,
Rare
$BAD
• WINS: Large, Rare
• LOSSES: Large, Frequent
$
Iowa Gambling Task
BAD• WINS: Large,
Rare• LOSSES: Large,
Frequent
$
Bechara 2008
What happens if there is PFC dysfunction?
Bechara 2008
What happens if there is PFC dysfunction?
Control
Cocaine Abuser
What happens if there is PFC dysfunction?
Control
Cocaine Abuser
What happens if there is PFC dysfunction?
Control
Cocaine Abuser
Summary:
Why is it so difficult to quit?
Memory
Control
Drive
Non-Addicted
WANT
Memory
Addicted
Control
WANT Drive
STOP GO
Thank you